Details for Patent: 8,303,944
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Title: | Hepatitis C virus inhibitors |
Abstract: | The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection. |
Inventor(s): | Bachand; Carol (Candiac, CA), Belema; Makonen (North Haven, CT), Deon; Daniel H. (Brossard, CA), Good; Andrew C. (Wallingford, CT), Goodrich; Jason (Meriden, CT), James; Clint A. (Longueuil, CA), Lavoie; Rico (Candiac, CA), Lopez; Omar D. (Wallingford, CT), Martel; Alain (Delson, CA), Meanwell; Nicholas A. (East Hampton, CT), Nguyen; Van N. (Meriden, CT), Romine; Jeffrey Lee (Meriden, CT), Ruediger; Edward H. (Greenfield Park, CA), Snyder; Lawrence B. (Killingworth, CT), St. Laurent; Denis R. (Newington, CT), Yang; Fukang (Madison, CT), Langley; David R. (Meriden, CT), Wang; Gan (Wallingford, CT), Hamann; Lawrence G. (North Grafton, MA) |
Assignee: | Bristol-Myers Squibb Company (Princeton, NJ) |
Filing Date: | Feb 13, 2008 |
Application Number: | 12/030,232 |
Claims: | 1. A compound selected from methyl ((1S)-2-((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-(N-(methoxycarbonyl)-L-alan- yl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)-4-biphenylyl)-1H-imidaz- ol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)-1-methyl-2-oxoethyl)carbamate; dimethyl (4,4'-biphenyldiylbis(1H-imidazole-4,2-diyl(1R,3S,5R)-2-azabicyc- lo[3.1.0]hexane-3,2-diyl((2S)-1-oxo-1,2-butanediyl)))biscarbamate; methyl (2-((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-(((methoxycarbonyl)amino)acetyl)- -2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)-4-biphenylyl)-1H-imidazol-- 2-yl)-2-azabicyclo[3.1.0]hex-2-yl)-2-oxoethyl)carbamate; dimethyl (4,4'-biphenyldiylbis(1H-imidazole-4,2-diyl(1R,3S,5R)-2-azabicyclo[3.1.0]- hexane-3,2-diyl((1S)-1-cyclopropyl-2-oxo-2,1-ethanediyl)))biscarbamate; dimethyl (4,4'-biphenyldiylbis(1H-imidazole-4,2-diyl(1R,3S,5R)-2-azabicyc- lo[3.1.0]hexane-3,2-diyl((1R)-2-oxo-1-phenyl-2,1-ethanediyl)))biscarbamate- ; methyl ((1S)-1-(((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-acetyl-2-azabicycl- o[3.1.0]hex-3-yl)-1H-imidazol-4-yl)-4-biphenylyl)-1H-imidazol-2-yl)-2-azab- icyclo[3.1.0]hex-2-yl)carbonyl)-2-methylpropyl)carbamate; methyl ((1S)-2-methyl-1-(((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-(5-((3aS,4S,6aR)-- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)-2-azabicyclo[3.1.0- ]hex-3-yl)-1H-imidazol-4-yl)-4-biphenylyl)-1H-imidazol-2-yl)-2-azabicyclo[- 3.1.0]hex-2-yl)carbonyl-2-methylpropyl)carbamate; tert-butyl ((1S)-1-(((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-((2S)-2-((tert-butoxycarbo- nyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl- )-4-biphenylyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)carbonyl)-2-- methylpropyl)carbamate; N-((1S)-1-(((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-((2S)-2-((cyclopropylcar- bonyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-- yl)-4-biphenylyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)carbonyl)-- 2-methylpropyl)cyclopropanecarbamate; tert-butyl ((1R)-1-(((1R,3S,5R)-3-(4-(4'-(2-((1R,3S,5R)-2-((2R)-2-((tert-butoxycarbo- nyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl- )-4-biphenylyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)carbonyl)-2-- methylpropyl)carbamate; and N,N'-(4,4'-biphenyldiylbis(1H-imidazole-4,2-diyl(1R,3S,5R)-2-azabicyclo[3- .1.0]hexane-3,2-diyl((2S)-3-methyl-1-oxo-1,2-butanediyl)))di(2-pyrimidinam- ine); or a pharmaceutically acceptable salt thereof. 2. A composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 3. The composition of claim 2 further comprising one or two additional compounds having anti-HCV activity. 4. The composition of claim 3 wherein at least one of the additional compounds is an interferon or a ribavirin. 5. The composition of claim 4 wherein the interferon is selected from interferon alpha 2B, pegylated interferon alpha, consensus interferon, interferon alpha 2A, and lymphoblastiod interferon tau. 6. The composition of claim 3 wherein at least one of the additional compounds is selected from interleukin 2, interleukin 6, interleukin 12, a compound that enhances the development of a type 1 helper T cell response, interfering RNA, anti-sense RNA, Imiqimod, ribavirin, an inosine 5'-monophospate dehydrogenase inhibitor, amantadine, and rimantadine. 7. The composition of claim 3 wherein at least one of the additional compounds is effective to inhibit the function of a target selected from HCV metalloprotease, HCV serine protease, HCV polymerase, HCV helicase, HCV NS4B protein, HCV entry, HCV assembly, HCV egress, HCV NS5A protein, and IMPDH for the treatment of an HCV infection. 8. A method of relieving or causing regression of an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof. 9. The method of claim 8 further comprising administering one or two additional compounds having anti-HCV activity prior to, after or simultaneously with the compound of claim 2, or a pharmaceutically acceptable salt thereof. 10. The method of claim 9 wherein at least one of the additional compounds is an interferon or a ribavirin. 11. The method of claim 10 wherein the interferon is selected from interferon alpha 2B, pegylated interferon alpha, consensus interferon, interferon alpha 2A, and lymphoblastiod interferon tau. 12. The method of claim 9 wherein at least one of the additional compounds is selected from interleukin 2, interleukin 6, interleukin 12, a compound that enhances the development of a type 1 helper T cell response, interfering RNA, anti-sense RNA, Imiqimod, ribavirin, an inosine 5'-monophospate dehydrogenase inhibitor, amantadine, and rimantadine. 13. The method of claim 9 wherein at least one of the additional compounds is effective to inhibit the function of a target selected from HCV metalloprotease, HCV serine protease, HCV polymerase, HCV helicase, HCV NS4B protein, HCV entry, HCV assembly, HCV egress, HCV NS5A protein, and IMPDH for the treatment of an HCV infection. |